The case against the prion appears to solidifying. A report in today's Nature shows that prion forms found in apparently anomalous prion diseases-those that do not feature the abnormally folded prion protein (PrP[Sc])-are likely to represent the common final path to neurodegeneration in all the spongiform encephalopathies ("mad cow" disease, Creutzfeldt-Jacob disease, etc).

There have been lingering doubts about the prion hypothesis because genetic forms of the spongiform encephalopathies, both animal and human, do not produce PrP[Sc], the form of the protein that has been cited as characteristic of these diseases. On the other hand, these anomalous diseases do feature an abnormal form of the prion protein termed [Ctm]PrP.

Vishwanath Lingappa, Ramanujan Hegde and colleagues at the University of California, San Francisco first identified [Ctm]PrP, and over the past two years they have shown that it is an abnormal form that becomes trapped in the membrane of the endoplasmic reticulum. They have also shown that the propensity for mice to develop spongiform encephalopathy is related in a dose-responsive way to the levels of [Ctm]PrP expressed. In the present paper, they demonstrate that the ability of PrP[Sc] to produce disease is directly related to the levels of [Ctm]PrP expressed. Their results suggest that each of the two abnormal forms of prion protein is able to directly or indirectly influence the metabolism of the other.

The authors suggest that these results are consistent with a model of prion diseases where abnormally folded prion (PrP[Sc]) is one route, but not the only one, to neurodegeneration that is ultimately caused by [Ctm]PrP (by an a still unknown mechanism).—Hakon Heimer


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Primary Papers

  1. . Transmissible and genetic prion diseases share a common pathway of neurodegeneration. Nature. 1999 Dec 16;402(6763):822-6. PubMed.
  2. . Spongiform encephalopathies. Breech-birth prions. Nature. 1999 Dec 16;402(6763):737, 739. PubMed.